1. Field of the Invention
This invention relates generally to new immunomodulatory peptides and particularly to analogs of the peptide thymopentin which have greatly increased potency.
2. Description of the Art
U.S. Pat. Nos. 4,190,646 and 4,261,886 disclose various pentapeptides having activity similar to the long chain polypeptide known as thymopoietin, which is described in U.S. Pat. Nos. 4,002,740 and 4,077,949. Thymopoietin selectively stimulates the differentiation of T cells. The pentapeptide disclosed in the U.S. Pat. No. 4,190,646 which has the sequence H-ARG-LYS-ASP-VAL-THY-OH, is known as the thymopoietin pentapeptide or "thymopentin". The biological activity of certain of these peptides is described in an article by M. E. Weksler, et al., J. Exp. Med. 148: 996-1006 (1978). The above U.S. patents and article are incorporated herein by reference. U.S. Pat. Nos. 4,361,673 and 4,420,424 also disclose various peptides asserted to have activity similar to thymopoietin. A peptide of similar structure isolated from bovine spleen and termed "splenin" is described in Audhya, et al., Biochemistry, 20, 6195-6200 (1981) and Proc. Nat. Acad. Sci. (USA), 81, 2847-2849 (May 1984). This material stimulates induction of both T cells and B cells.
Certain enzyme-resistant immunomodulatory peptides are disclosed in our copending application Ser. No. 553,281, filed Nov. 18, 1983, which is incorporated herein by reference.
Thymopentin has been shown to exert a modulatory effect on the immune system of animals and humans and is thus useful for treatment of diseases involving defects in immune function, whether such defects are manifested as deficiencies or excesses of immune function. See for example Audhya, T. and Goldstein, G., Int. J. Pept. Protein Res., 22, 568-572 (1983); Aiuti, et al., Lancet 1:551-555 (1983); and Levinsky, et al., in "Primary Immunodeficiency Diseases", Wedgewood, Rosen, and Paul, eds, 19, 273-276 (1983). Reference is made to these articles and to the above-described patents and article for a discussion of other background material and the biological processes involved in the present invention.
The present invention provides peptides and peptide compositions which are surprisingly more potent than thymopentin or splenin and thus offer significant advantages in the treatment of immune defects.